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In this study, we characterized a broad range of <jats:styled-content style=\"fixed-case\">MCL<\/jats:styled-content> cell lines and primary <jats:styled-content style=\"fixed-case\">MCL<\/jats:styled-content> cells with respect to the response to the <jats:styled-content style=\"fixed-case\">BTK<\/jats:styled-content> inhibitor, ibrutinib, and compared it with the response to the protein kinase C (<jats:styled-content style=\"fixed-case\">PKC<\/jats:styled-content>) inhibitor, sotrastaurin. At clinically relevant concentrations, each drug induced potent cell death only in the <jats:styled-content style=\"fixed-case\">REC<\/jats:styled-content>\u20101 cell line, which was accompanied by robust inhibition of <jats:styled-content style=\"fixed-case\">AKT<\/jats:styled-content> and <jats:styled-content style=\"fixed-case\">ERK<\/jats:styled-content>1\/<jats:styled-content style=\"fixed-case\">ERK<\/jats:styled-content>2 (<jats:styled-content style=\"fixed-case\">ERK<\/jats:styled-content>1\/2, also termed <jats:styled-content style=\"fixed-case\">MAPK<\/jats:styled-content>3\/<jats:styled-content style=\"fixed-case\">MAPK<\/jats:styled-content>1) phosphorylation. In sensitive <jats:styled-content style=\"fixed-case\">REC<\/jats:styled-content>\u20101 cells, the drug\u2010mediated impaired phosphorylation was obvious on the levels of B\u2010cell receptor\u2010induced and basal phosphorylation. Similar results were obtained in primary <jats:styled-content style=\"fixed-case\">MCL<\/jats:styled-content> cells with ibrutinib and in a subset with sotrastaurin. The various drug\u2010resistant <jats:styled-content style=\"fixed-case\">MCL<\/jats:styled-content> cell lines showed very distinct responses in terms of basal <jats:styled-content style=\"fixed-case\">AKT<\/jats:styled-content> and <jats:styled-content style=\"fixed-case\">ERK<\/jats:styled-content>1\/2 phosphorylation. Interestingly, targeting <jats:styled-content style=\"fixed-case\">PKC<\/jats:styled-content> and <jats:styled-content style=\"fixed-case\">BTK<\/jats:styled-content> at the same time led to ibrutinib\u2010mediated rescue of a weak sotrastaurin\u2010induced apoptosis in <jats:styled-content style=\"fixed-case\">MINO<\/jats:styled-content> cells. Additional targeting of <jats:styled-content style=\"fixed-case\">AKT<\/jats:styled-content> sensitized <jats:styled-content style=\"fixed-case\">MINO<\/jats:styled-content> cells to inhibitor\u2010mediated cytotoxicity. In summary, <jats:styled-content style=\"fixed-case\">MCL<\/jats:styled-content> cells are heterogeneous in their response to <jats:styled-content style=\"fixed-case\">BTK<\/jats:styled-content> or <jats:styled-content style=\"fixed-case\">PKC<\/jats:styled-content> inhibition, indicating the need for even more individualized targeted treatment approaches in subsets of <jats:styled-content style=\"fixed-case\">MCL<\/jats:styled-content> patients.<\/jats:p>","DOI":"10.1111\/bjh.13973","type":"journal-article","created":{"date-parts":[[2016,2,26]],"date-time":"2016-02-26T01:54:50Z","timestamp":1456451690000},"page":"394-403","update-policy":"http:\/\/dx.doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Targeting protein kinase C in mantle cell lymphoma"],"prefix":"10.1111","volume":"173","author":[{"given":"Hilka","family":"Rauert\u2010Wunderlich","sequence":"first","affiliation":[{"name":"Institute of Pathology University of W\u00fcrzburg and 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